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Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation

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Pinzan, Camila Figueiredo ; Valero, Clara ; de Castro, Patricia Alves ; da Silva, Jefferson Luiz ; Earle, Kayleigh ; Liu, Hong ; Horta, Maria Augusta Crivelente ; Kniemeyer, Olaf ; Kruger, Thomas ; Pschibul, Annica ; Comert, Derya Nur ; Heinekamp, Thorsten ; Brakhage, Axel A. ; Steenwyk, Jacob L. ; Mead, Matthew E. ; Hermsdorf, Nico ; Filler, Scott G. ; da Rosa-Garzon, Nathalia Gonsales ; Delbaje, Endrews ; Bromley, Michael J. ; Cabral, Hamilton ; Diehl, Camila ; Angeli, Claudia B. ; Palmisano, Giuseppe ; Ibrahim, Ashraf S. ; Rinker, David C. ; Sauters, Thomas J. C. ; Steffen, Karin ; Gumilang, Adiyantara ; Rokas, Antonis ; Gago, Sara ; dos Reis, Thaila F. ; Goldman, Gustavo H.
Total Authors: 33
Document type: Journal article
Source: NATURE MICROBIOLOGY; v. 9, n. 10, p. 30-pg., 2024-08-27.
Abstract

Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1 beta, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection. (AU)

FAPESP's process: 22/13603-4 - Large-scale data integration to study gene expression dynamics of Aspergillus fumigatus metabolic pathways related to caspofungin's antifungal action
Grantee:Endrews Delbaje
Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 22/08796-8 - Molecular characterization of putative effector proteins in the human fungal pathogen Aspergillus fumigatus
Grantee:Camila Diehl da Rosa
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
Grantee:Giuseppe Palmisano
Support Opportunities: Regular Research Grants
FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
Grantee:Giuseppe Palmisano
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
Grantee:Giuseppe Palmisano
Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 21/04977-5 - The identification of new pathways and compounds that can enhance caspofungin activity against Aspergillus fumigatus
Grantee:Gustavo Henrique Goldman
Support Opportunities: Research Projects - Thematic Grants